The population around the world is constantly coming in contact with viruses through social and/or accidental means. Those infected by the virus can in many cases be treated with conventional antivirals. However, some of the viruses such as hepatitis, HIV or herpes result in serious illnesses. Furthermore, many of the viruses mutate and become resistant to antibiotics. Therefore, it is desirable to kill the virus before the party is infected. It is therefore desirable to prophylactically protect a host from contamination by the virus.
The virus easily invades a host through mucous membranes or openings in the skin. The skin is generally a good barrier against invasion by microorganisms and washing can eliminate the microorganisms. However, there are times when a party who has come into contact with a microorganism cannot wash or treat an area of the body so that it is necessary to provide antiviral/spermicidal protection before and/or during contact in an area where infection can occur.
Due to the variety and complexity of the potential outcomes of sexual activity, including pregnancy, disease and discomfort, agents which can be used alone or in conjunction with condoms will require functionality that cannot reasonably be derived from a singular entity. For example, standard lubricants with detergents, specifically Nonoxynol-9 (N-9), provide protection against pregnancy and a variety of sexually transmitted diseases (STDs). The detergents also have a drawback in that in high concentrations and/or high frequency of use, they have the potential to cause irritation of mucosal tissue.
It is desirable to improve the efficacy of the agents while reducing the deleterious side effects. The primary focus is on strategies that can be used with or without condoms, but must address both pregnancy and disease prevention. There are other agents effective as spermicides and microbicides including other detergents, buffering agents and even selective inorganic agents. Combinations of these can increase the breadth of activity against STDs. For example, the use of buffering agents is highly effective against pregnancy, but of limited value in protection against STDs.
A third factor in the design of effective therapies includes the incorporation of agents selected to not only reduce possible irritation caused by one or more of the other agents, but to even ameliorate existing irritation.
One additional factor is to specifically include strategies directly targeting HIV. Due to the significance of HIV infection, specific agents should also be added to bolster the efficacy. Some of the agents already being considered for the amelioration of irritation are also effective binding agents for the same cell receptors that HIV targets. In addition, HIV-specific agents, while still in the early stages of testing, can be incorporated in future formulations.
In order for a composition to be capable of universal use it is required that it meet at least the following characteristics.
1. The composition is spermicidal/viricidal.
2. The composition can be used in sensitive areas, for example, mucosal membranes, therefore it must be non-irritating.
3. The composition must form a barrier.
Advantageously, the pH is adjusted for each site of use. There exists a specific need for improving methods and compositions for preventing sexually transmitted diseases (STDs) and unwanted pregnancies both with and without condoms. This objective should be realized by maintaining normal and protective vaginal flora that play a role in the prevention of vaginitis, vaginosis, and urinary tract infections. The present invention is also based on the realization that a method providing rapid and reliable control of vaginal pH could provide a highly effective, yet highly physiologic means to achieve these goals.
The most effective contraceptive methods (sterilization, intrauterine devices, and contraceptive hormones) provide no protection against STDs. Barrier contraceptive methods such as condoms, diaphragms, and vaginal spermicides help prevent STD transmission by interposing a mechanical or chemical barrier between the female and the male, most importantly between the uterine cervix and the glans and urethral orifice of the penis. This barrier action is effective because secretions from the sites (cervical mucus and semen) are the most important sources of STD pathogens and also because these sites are the most susceptible targets for many STD pathogens. However, current barrier methods suffer from poor acceptance and therefore poor efficacy because they are inconvenient to use, and/or have undesirable toxicity. Male and female condoms are cumbersome to use and may reduce sexual pleasure and intimacy. Vaginal spermicides can erode the mucosa if used too frequently, and even with infrequent use, can disrupt the protective normal vaginal flora.
The pH of a healthy vagina is mildly acidic (pH 3.5-4.5) and this acidity is thought to be generated by the production of lactic acid by lactobacilli, which form a major component of the healthy vaginal flora. Together with other factors, this acid pH is widely recognized to prevent overgrowth of undesirable microbes (Candida, harmful anaerobes, and bacteria that may cause urinary tract infections) and encourages the continued dominance of lactobacilli which, in addition to mild acidity, provide other protective mechanisms such as production of hydrogen peroxide.
It is also known that sperm are inactivated by the mild acidity of the healthy vagina, and acid substances have been used as home made vaginal contraceptives for centuries. More recently it has been recognized that many sexually transmitted disease pathogens, Neisseria gonorrhea, Treponema palladium, Haemophilus ducreyi, and most or all enveloped STD viruses including herpes simplex virus, cytomegalovirus, and human immunodeficiency virus, are also inhibited or inactivated by mild acidic pH. However, semen contains a potent alkaline buffering capacity that neutralizes the vaginal acidity for a period of many hours after intercourse. This alkaline buffering capacity enables sperm to swim from the vagina into the cervix and upper genital tract.
Unfortunately, STD pathogens in genital secretions can also exploit this period of neutral vaginal pH, since it allows time for them to reach and infect their target cells. If this semen-induced neutralization of vaginal acidity could be promptly and reliably overcome, both contraception and STD prevention could be achieved by a method that closely mimics the normal physiological state of the vagina.
In addition, the elevated pH also allows certain strains of Staphylococcus aureus to produce shock toxin I, whereas production of this toxin is completely inhibited at acidic pH.ltoreq.5.0. Thus, loss of protective acidity may result in staphylococcal toxic shock syndrome, candida vaginitis, bacterial vaginosis, or urinary tract infection.
The use of cellulosic binders such as methyl cellulose, hydroxymethylcellulose, and the like in mucosal areas can cause irritation over long periods of time.
U.S. Pat. No. 5,617,877 to Moench et al. discloses a contraceptive composition comprising a spermicide and cellulosic delivery system over which the present invention provides an advantage.